Type 1 Diabetes Induces Severe Cognitive Decline and Neurodegeneration, While Type 2 Diabetes Drives Oxidative Stress and Inflammation in Rat Brains

The long-term impact of Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) on specific brain regions like the hippocampus and prefrontal cortex (PFC) remains incompletely understood, despite growing evidence linking diabetes to cognitive impairment. Current understanding often generalizes diabetic encephalopathy, overlooking potential type-specific neurobiological differences. This study addresses the gap by comparing chronic neurobiological, cognitive, and behavioral consequences of prolonged hyperglycemia in experimental T1D and T2D models, aiming to identify distinct patterns of dysfunction relevant to diabetic encephalopathy.

Adult rats were divided into three groups: Sham, T1D, and T2D. T1D was induced by a single intraperitoneal injection of streptozotocin (STZ). T2D was established by administering nicotinamide (NA) 15 minutes prior to STZ injection. Behavioral and cognitive functions were assessed during the final phase of the 100-day experimental period. Post-testing, blood samples were collected for biochemical analyses. The PFC and hippocampus were then dissected to evaluate oxidative stress markers, inflammatory mediators, acetylcholinesterase (AChE) activity, BDNF levels, and Na⁺/K⁺-ATPase activity. Neuronal integrity was also assessed via Nissl staining.

After 100 days of hyperglycemia, both T1D and T2D rats displayed significant functional and structural alterations in the hippocampus and PFC. Distinct patterns of dysfunction emerged between the two diabetes types. T2D was significantly associated with pronounced oxidative stress and inflammatory responses, which correlated with anxiety- and depression-like behaviors (P < 0.05). This suggests a primary role for neuroinflammation and oxidative damage in T2D-related mood and behavioral changes. In contrast, T1D induced more extensive cognitive decline, neurochemical, and structural disruption. This included marked BDNF depletion, a significant Na⁺/K⁺-ATPase reduction, and elevated AChE activity (P < 0.05).